van der Wal A C, Becker A E, van der Loos C M, Tigges A J, Das P K
Department of Cardiovascular Pathology, University of Amsterdam, The Netherlands.
Coron Artery Dis. 1994 Jun;5(6):463-9.
The morphology of advanced atherosclerotic plaques varies from solid fibrous lesions, considered essentially stable, to lipid-rich lesions with large atheromas prone to rupture. The latter situation is often associated with large amounts of foam cells. An in-situ inflammatory process influenced by activated T cells and macrophages can be demonstrated in atherosclerotic plaques; however, the relationship between the inflammation and clinically relevant morphological types has not yet been investigated. A study of plaque morphology, focusing on the relationship between inflammatory cells, smooth muscle cells, and the collagen matrix, on the one hand, and the 'classic' plaque morphologies (fibrous versus lipid-rich), on the other, may shed light on this concept.
Immunocytochemical techniques were used in combination with connective tissue stains to study the topographic distribution of smooth muscle cells, collagen, and inflammatory cells in different morphologic types of advanced atherosclerotic plaques in aortic and carotid arteries obtained at autopsy.
Lesions with an inconspicuous lipid core were defined as fibrous (n = 7). They contained a dense collagen matrix and the dominant cell type was the smooth muscle cell; lymphocytes and macrophages were sparse. Lesions with a large lipid core were defined as lipid-rich (n = 13). They contained a thin fibrous cap with a loosely arranged matrix dominated by macrophages and T cells. Most lesions (n = 21), however, had a morphology that ranged between fibrous and lipid-rich. The cellular components consisted either of mixed smooth muscle and inflammatory cells or of local distinct zones of inflammatory cells within a fibrous cap otherwise dominated by smooth muscle cells and collagen. Thus, zones of severe inflammation were invariably associated with dissolution of the connective tissue matrix and abundant human leukocyte antigen-DR expression on inflammatory cells and the remaining smooth muscle cells.
Our observations support the concept that inflammatory mechanisms modulate plaque morphology, by promoting either synthesis or lysis of the fibrous cap. Our hypothesis is that fibrous and atheromatous lesions are essentially interchangeable.
晚期动脉粥样硬化斑块的形态各异，从本质上被认为相对稳定的实性纤维性病变，到富含脂质且易破裂的大粥样瘤病变。后一种情况通常与大量泡沫细胞相关。在动脉粥样硬化斑块中可证实存在受活化T细胞和巨噬细胞影响的原位炎症过程；然而，炎症与临床相关形态学类型之间的关系尚未得到研究。一项针对斑块形态学的研究，一方面关注炎症细胞、平滑肌细胞和胶原基质之间的关系，另一方面关注“经典”的斑块形态（纤维性与富含脂质），可能会阐明这一概念。
采用免疫细胞化学技术并结合结缔组织染色，研究在尸检时获得的主动脉和颈动脉中不同形态学类型的晚期动脉粥样硬化斑块中平滑肌细胞、胶原和炎症细胞的拓扑分布。
脂质核心不明显的病变被定义为纤维性病变（n = 7）。它们含有致密的胶原基质，主要细胞类型是平滑肌细胞；淋巴细胞和巨噬细胞稀少。脂质核心大的病变被定义为富含脂质的病变（n = 13）。它们含有薄的纤维帽，其基质排列松散，以巨噬细胞和T细胞为主。然而，大多数病变（n = 21）的形态介于纤维性和富含脂质之间。细胞成分要么由平滑肌细胞和炎症细胞混合组成，要么在以平滑肌细胞和胶原为主的纤维帽内有局部明显的炎症细胞区域。因此，严重炎症区域总是与结缔组织基质的溶解以及炎症细胞和剩余平滑肌细胞上丰富的人类白细胞抗原-DR表达相关。
我们的观察结果支持这样的概念，即炎症机制通过促进纤维帽的合成或溶解来调节斑块形态。我们的假设是纤维性病变和粥样瘤性病变本质上是可相互转换的。
